MCID: SCC001
MIFTS: 52

Succinic Semialdehyde Dehydrogenase Deficiency malady

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Succinic Semialdehyde Dehydrogenase Deficiency

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Aliases & Descriptions for Succinic Semialdehyde Dehydrogenase Deficiency:

Name: Succinic Semialdehyde Dehydrogenase Deficiency 50 11 22 46 23 24 13 52 68 12 66
4-Hydroxybutyric Aciduria 11 22 46 23 24 52 68
Gamma-Hydroxybutyric Aciduria 11 22 23 24 52 68
Ssadh Deficiency 22 46 23 24 52 68
Succinate Semialdehyde Dehydrogenase Deficiency 68 25
Gaba Metabolic Defect 46 68
 
Succinic Semialdehyde Dehydrogenase 12
Gamma-Hydroxybutyric Acidemia 24
Gamma-Hydroxybutyricaciduria 46
4-Hydroxybutyricaciduria 24
Ssadhd 68
Ssadh 11

Characteristics:

Orphanet epidemiological data:

52
succinic semialdehyde dehydrogenase deficiency:
Inheritance: Autosomal recessive; Age of onset: Childhood,Infancy,Neonatal; Age of death: adult

HPO:

62
succinic semialdehyde dehydrogenase deficiency:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset, phenotypic variability


Classifications:



External Ids:

OMIM50 271980
Disease Ontology11 DOID:0060175
Orphanet52 ORPHA22
ICD10 via Orphanet29 E72.8
MedGen35 C0268631
MeSH37 D000592

Summaries for Succinic Semialdehyde Dehydrogenase Deficiency

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Genetics Home Reference:24 Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.

MalaCards based summary: Succinic Semialdehyde Dehydrogenase Deficiency, also known as 4-hydroxybutyric aciduria, is related to epilepsy and hypotonia, and has symptoms including muscular hypotonia, incoordination and cognitive impairment. An important gene associated with Succinic Semialdehyde Dehydrogenase Deficiency is ALDH5A1 (Aldehyde Dehydrogenase 5 Family Member A1), and among its related pathways are Valproic Acid Pathway, Pharmacodynamics and Cyclophosphamide Pathway, Pharmacodynamics. Affiliated tissues include eye, brain and globus pallidus.

Disease Ontology:11 A gamma-amino butyric acid metabolism disorder that is characterized by a deficiency of succinic semialdehyde dehydrogenase resulting in elevated levels of gamma-hydroxybutyric acid.

NIH Rare Diseases:46 Succinic semialdehyde dehydrogenase (ssadh) deficiency is disorder that can cause a variety of neurological and neuromuscular problems. the signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems. ssadh deficiency is caused by mutations in the aldh5a1 gene and is inherited in an autosomal recessive manner. management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues. last updated: 9/25/2013

UniProtKB/Swiss-Prot:68 Succinic semialdehyde dehydrogenase deficiency: A rare inborn error of 4-aminobutyric acid (GABA) metabolism, which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is clinically characterized by developmental delay, hypotonia, mental retardation, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances.

OMIM:50 Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive neurologic disorder in which an... (271980) more...

Wikipedia:69 Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or... more...

GeneReviews summary for NBK1195

Related Diseases for Succinic Semialdehyde Dehydrogenase Deficiency

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Graphical network of the top 20 diseases related to Succinic Semialdehyde Dehydrogenase Deficiency:



Diseases related to succinic semialdehyde dehydrogenase deficiency

Symptoms for Succinic Semialdehyde Dehydrogenase Deficiency

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Symptoms by clinical synopsis from OMIM:

271980

Clinical features from OMIM:

271980

Symptoms:

 52 (show all 9)
  • behavioral abnormality
  • intellectual disability
  • ataxia
  • muscular hypotonia
  • global developmental delay
  • abnormality of metabolism/homeostasis
  • generalized tonic-clonic seizures
  • generalized myoclonic seizures
  • status epilepticus

HPO human phenotypes related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show all 26)
id Description Frequency HPO Source Accession
1 muscular hypotonia hallmark (90%) HP:0001252
2 incoordination hallmark (90%) HP:0002311
3 cognitive impairment hallmark (90%) HP:0100543
4 seizures typical (50%) HP:0001250
5 abnormality of eye movement HP:0000496
6 psychosis HP:0000709
7 autism HP:0000717
8 aggressive behavior HP:0000718
9 hallucinations HP:0000738
10 anxiety HP:0000739
11 delayed speech and language development HP:0000750
12 hyperactivity HP:0000752
13 intellectual disability HP:0001249
14 ataxia HP:0001251
15 muscular hypotonia HP:0001252
16 global developmental delay HP:0001263
17 hyporeflexia HP:0001265
18 motor delay HP:0001270
19 abnormality of metabolism/homeostasis HP:0001939
20 generalized tonic-clonic seizures HP:0002069
21 absence seizures HP:0002121
22 generalized myoclonic seizures HP:0002123
23 status epilepticus HP:0002133
24 eeg abnormality HP:0002353
25 hyperkinesis HP:0002487
26 self-injurious behavior HP:0100716

UMLS symptoms related to Succinic Semialdehyde Dehydrogenase Deficiency:


ataxia, seizures

Drugs & Therapeutics for Succinic Semialdehyde Dehydrogenase Deficiency

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Drugs for Succinic Semialdehyde Dehydrogenase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1
TaurineNutraceutical26107-35-71123
Synonyms:
1-Aminoethane-2-sulfonate
1-Aminoethane-2-sulfonic acid
2-Aminoethanesulfonate
2-Aminoethanesulfonic acid
2-Aminoethylsulfonate
2-Aminoethylsulfonic acid
 
2-Sulfoethylamine
Aminoethylsulfonate
Aminoethylsulfonic acid
Taurine
b-Aminoethylsulfonate
b-Aminoethylsulfonic acid
beta-Aminoethylsulfonate
beta-Aminoethylsulfonic acid

Interventional clinical trials:

idNameStatusNCT IDPhase
1Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase DeficiencyRecruitingNCT02019667Phase 2
2PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase DeficiencyCompletedNCT00246870
3Brain Excitability in Patients With Succinic Semialdehyde Dehydrogenase DeficiencyCompletedNCT00132366
4Taurine Therapy for SSADH DeficiencyCompletedNCT01608178

Search NIH Clinical Center for Succinic Semialdehyde Dehydrogenase Deficiency

Genetic Tests for Succinic Semialdehyde Dehydrogenase Deficiency

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Genetic tests related to Succinic Semialdehyde Dehydrogenase Deficiency:

id Genetic test Affiliating Genes
1 Succinate-Semialdehyde Dehydrogenase Deficiency25
2 Succinic Semialdehyde Dehydrogenase Deficiency23 ALDH5A1

Anatomical Context for Succinic Semialdehyde Dehydrogenase Deficiency

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MalaCards organs/tissues related to Succinic Semialdehyde Dehydrogenase Deficiency:

34
Eye, Brain, Globus pallidus, Liver

Animal Models for Succinic Semialdehyde Dehydrogenase Deficiency or affiliated genes

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Publications for Succinic Semialdehyde Dehydrogenase Deficiency

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Articles related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show top 50)    (show all 75)
idTitleAuthorsYear
1
Biomarkers in a Taurine Trial for Succinic Semialdehyde Dehydrogenase Deficiency. (27338723)
2016
2
A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression. (27117035)
2016
3
Succinic semialdehyde dehydrogenase deficiency (SSADHD): Pathophysiological complexity and multifactorial trait associations in a rare monogenic disorder of GABA metabolism. (27311541)
2016
4
Psychomotor delay, hypotonia, and behavioural disorders: A case of succinic semialdehyde dehydrogenase deficiency. (26964512)
2016
5
Acute Infantile Encephalopathy as Presentation of Succinic Semialdehyde Dehydrogenase Deficiency. (27268762)
2016
6
Succinic semialdehyde dehydrogenase deficiency of four Chinese patients and prenatal diagnosis for three fetuses. (26220405)
2015
7
A Novel Mutation of ALDH5A1 Gene Associated With Succinic Semialdehyde Dehydrogenase Deficiency. (25246302)
2014
8
Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA. (24523482)
2014
9
Analysis of ALDH5A1 gene mutation in a Chinese Han family with succinic semialdehyde dehydrogenase deficiency]. (23926001)
2013
10
Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (22739941)
2013
11
A novel ALDH5A1 mutation in a patient with succinic semialdehyde dehydrogenase deficiency. (22437753)
2012
12
Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (21664777)
2011
13
Neuropathology in succinic semialdehyde dehydrogenase deficiency. (20304328)
2010
14
Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency. (20445195)
2010
15
Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. (19667317)
2009
16
Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde dehydrogenase deficiency patients. (18622364)
2008
17
Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (18514581)
2008
18
'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'. (18811705)
2008
19
Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. (17438226)
2007
20
Enzymatic and metabolic evidence for a region specific mitochondrial dysfunction in brains of murine succinic semialdehyde dehydrogenase deficiency (Aldh5a1-/- mice). (17303287)
2007
21
Clinical, cytogenetic and molecular characterization of a patient with combined succinic semialdehyde dehydrogenase deficiency and incomplete WAGR syndrome with obesity. (16545979)
2006
22
Proton MR spectroscopy in succinic semialdehyde dehydrogenase deficiency. (15037717)
2004
23
The molecular basis of succinic semialdehyde dehydrogenase deficiency in one family. (15059623)
2004
24
Succinic semialdehyde dehydrogenase deficiency (SSADH) (4-hydroxybutyric aciduria, gamma-hydroxybutyric aciduria). (15341910)
2004
25
Neurodevelopmental pattern of succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria). (15287248)
2004
26
Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. (15016427)
2004
27
Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. (15582027)
2004
28
Liver-directed adenoviral gene transfer in murine succinate semialdehyde dehydrogenase deficiency. (15093183)
2004
29
Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. (12743223)
2003
30
Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. (12891656)
2003
31
Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency. (12829002)
2003
32
Succinic semialdehyde dehydrogenase deficiency in children and adults. (12891657)
2003
33
Rapid and sensitive detection of urinary 4-hydroxybutyric acid and its related compounds by gas chromatography-mass spectrometry in a patient with succinic semialdehyde dehydrogenase deficiency. (12127325)
2002
34
Neuroleptic malignant syndrome in a patient with succinic semialdehyde dehydrogenase deficiency. (11819156)
2002
35
A unique mouse model for succinic semialdehyde dehydrogenase deficiency with implications for gamma hydroxybutyrate intoxication. (11990378)
2002
36
Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T>A of the ALDH5A1 gene. (11901270)
2002
37
Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses. (11243727)
2001
38
MRI findings in succinic semialdehyde dehydrogenase deficiency. (10774997)
2000
39
Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). (9683595)
1998
40
The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients. (9093300)
1997
41
Seizures in a boy with succinic semialdehyde dehydrogenase deficiency treated with vigabatrin (gamma-vinyl-GABA). (8803774)
1996
42
Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency. (7564230)
1995
43
Pre- and postnatal diagnosis of succinic semialdehyde dehydrogenase deficiency using enzyme and metabolite assays. (7707697)
1994
44
Prenatal detection of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) (8464836)
1993
45
Succinic Semialdehyde Dehydrogenase Deficiency (20301374)
1993
46
Succinic semialdehyde dehydrogenase deficiency associated with combined 4-hydroxybutyric and dicarboxylic acidurias: potential for clinical misdiagnosis based on urinary organic acid profiling. (2926573)
1989
47
Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation. (3126356)
1987
48
Succinic semialdehyde dehydrogenase deficiency--a further case. (2433500)
1985
49
Succinic semialdehyde dehydrogenase deficiency. (6536727)
1984
50
Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism. (6627675)
1983

Variations for Succinic Semialdehyde Dehydrogenase Deficiency

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UniProtKB/Swiss-Prot genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

68 (show all 12)
id Symbol AA change Variation ID SNP ID
1ALDH5A1p.Cys93PheVAR_026199rs765561257
2ALDH5A1p.Gly176ArgVAR_026200
3ALDH5A1p.Cys223TyrVAR_026201
4ALDH5A1p.Thr233MetVAR_026202
5ALDH5A1p.Asn255SerVAR_026203rs145087265
6ALDH5A1p.Gly268GluVAR_026204rs375628463
7ALDH5A1p.Asn335LysVAR_026205
8ALDH5A1p.Pro382LeuVAR_026206
9ALDH5A1p.Pro382GlnVAR_026207
10ALDH5A1p.Gly409AspVAR_026208rs118203984
11ALDH5A1p.Val487GluVAR_026209
12ALDH5A1p.Gly533ArgVAR_026210rs72552284

Clinvar genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

5
id Gene Variation Type Significance SNP ID Assembly Location
1ALDH5A1ALDH5A1, IVS9, G-T, +1single nucleotide variantPathogenic
2ALDH5A1ALDH5A1, IVS5, G-A, +1single nucleotide variantPathogenic
3ALDH5A1NM_170740.1(ALDH5A1): c.612G> A (p.Trp204Ter)single nucleotide variantPathogenicrs118203982GRCh37Chr 6, 24505099: 24505099
4ALDH5A1NM_170740.1(ALDH5A1): c.1273C> T (p.Arg425Ter)single nucleotide variantPathogenicrs118203983GRCh37Chr 6, 24528285: 24528285
5ALDH5A1NM_001080.3(ALDH5A1): c.1226G> A (p.Gly409Asp)single nucleotide variantPathogenicrs118203984GRCh37Chr 6, 24528277: 24528277
6ALDH5A1NG_008161.1: g.31299_33753del2455deletionPathogenicGRCh37Chr 6, 24521495: 24523949
7ALDH5A1NM_170740.1(ALDH5A1): c.1382+1_1382+3delinsTTindelPathogenicrs875989801GRCh37Chr 6, 24528395: 24528397

Expression for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Search GEO for disease gene expression data for Succinic Semialdehyde Dehydrogenase Deficiency.

Pathways for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Pathways related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 24)
idSuper pathwaysScoreTop Affiliating Genes
1
Show member pathways
9.8ABAT, ALDH5A1
2
Show member pathways
9.6ALDH2, ALDH5A1
39.6ABAT, ALDH6A1
4
Show member pathways
9.3ALDH2, ALDH3A2
59.3ALDH2, ALDH3A2
6
Show member pathways
9.3ALDH2, ALDH3A2
7
Show member pathways
9.3ABAT, GAD1
8
Show member pathways
9.3ABAT, GAD1
9
Show member pathways
9.0ABAT, ALDH5A1, GAD1
10
Show member pathways
9.0ABAT, ALDH5A1, GAD1
118.9ALDH1B1, ALDH2, ALDH3A2
12
Show member pathways
8.9ALDH1B1, ALDH2, ALDH3A2
13
Show member pathways
8.9ALDH1B1, ALDH2, ALDH3A2
14
Show member pathways
8.9ALDH1B1, ALDH2, ALDH3A2
15
Show member pathways
8.9ALDH1B1, ALDH2, ALDH3A2
16
Show member pathways
8.9ALDH1B1, ALDH2, ALDH3A2
17
Show member pathways
8.9ALDH1B1, ALDH2, ALDH3A2
18
Show member pathways
8.9ALDH1B1, ALDH2, ALDH3A2
198.6ABAT, ALDH4A1, ALDH5A1, GAD1
20
Show member pathways
8.5ALDH1B1, ALDH2, ALDH3A2, ALDH4A1
21
Show member pathways
8.5ABAT, ALDH2, ALDH5A1, GAD1
22
Show member pathways
8.0ABAT, ALDH1B1, ALDH2, ALDH3A2, ALDH6A1
23
Show member pathways
7.2ABAT, ALDH1B1, ALDH2, ALDH3A2, ALDH6A1, GAD1
24
Show member pathways
6.1ABAT, AKR7A2, ALDH1B1, ALDH2, ALDH3A2, ALDH4A1

GO Terms for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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Cellular components related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1mitochondrial matrixGO:00057598.2ABAT, ALDH1B1, ALDH2, ALDH4A1, ALDH5A1, ALDH6A1
2mitochondrionGO:00057397.4ABAT, AKR7A2, ALDH1B1, ALDH3A2, ALDH4A1, ALDH5A1

Biological processes related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1gamma-aminobutyric acid catabolic processGO:000945010.5ABAT, ALDH5A1
2neurotransmitter catabolic processGO:004213510.4ABAT, ALDH5A1
3ethanol oxidationGO:000606910.1ALDH1B1, ALDH2
4ethanol catabolic processGO:000606810.1ALDH1B1, ALDH2
5cellular aldehyde metabolic processGO:000608110.1AKR7A2, ALDH3A2
6gamma-aminobutyric acid biosynthetic processGO:00094499.9ABAT, GAD1
7carbohydrate metabolic processGO:00059759.1AKR7A2, ALDH1B1, ALDH2
8oxidation-reduction processGO:00551148.2AKR7A2, ALDH3A2, ALDH4A1, ALDH6A1

Molecular functions related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1aldehyde dehydrogenase [NAD(P)+] activityGO:00040309.8ALDH2, ALDH3A2
2electron carrier activityGO:00090559.2AKR7A2, ALDH2, ALDH4A1
3pyridoxal phosphate bindingGO:00301709.0ABAT, GAD1
4aldehyde dehydrogenase (NAD) activityGO:00040298.1ALDH1B1, ALDH2, ALDH3A2, ALDH4A1, ALDH5A1, ALDH6A1

Sources for Succinic Semialdehyde Dehydrogenase Deficiency

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet